Blocking Signalopathic Events to Treat Cerebral Cavernous Malformations.
Trends Mol Med
; 26(9): 874-887, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32692314
ABSTRACT
Cerebral cavernous malformations (CCMs) are pathologies of the brain vasculature characterized by capillary-venous angiomas that result in recurrent cerebral hemorrhages. Familial forms are caused by a clonal loss of any of three CCM genes in endothelial cells, which causes the activation of a novel pathophysiological pathway involving mitogen-activated protein kinase and Krüppel-like transcription factor KLF2/4 signaling. Recent work has shown that cavernomas can undergo strong growth when CCM-deficient endothelial cells recruit wild-type neighbors through the secretion of cytokines. This suggests a treatment strategy based on targeting signalopathic events between CCM-deficient endothelial cells and their environment. Such approaches will have to consider recent evidence implicating 'third hits' from hypoxia-induced angiogenesis signaling or the microbiome in modulating the development of cerebral hemorrhages.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Hemangioma Cavernoso do Sistema Nervoso Central
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article